Navigation Links
Erasing a genetic mutation

CAMBRIDGE, MA -- Using a new gene-editing system based on bacterial proteins, MIT researchers have cured mice of a rare liver disorder caused by a single genetic mutation.

The findings, described in the March 30 issue of Nature Biotechnology, offer the first evidence that this gene-editing technique, known as CRISPR, can reverse disease symptoms in living animals. CRISPR, which offers an easy way to snip out mutated DNA and replace it with the correct sequence, holds potential for treating many genetic disorders, according to the research team.

"What's exciting about this approach is that we can actually correct a defective gene in a living adult animal," says Daniel Anderson, the Samuel A. Goldblith Associate Professor of Chemical Engineering at MIT, a member of the Koch Institute for Integrative Cancer Research, and the senior author of the paper.

The recently developed CRISPR system relies on cellular machinery that bacteria use to defend themselves from viral infection. Researchers have copied this cellular system to create gene-editing complexes that include a DNA-cutting enzyme called Cas9 bound to a short RNA guide strand that is programmed to bind to a specific genome sequence, telling Cas9 where to make its cut.

At the same time, the researchers also deliver a DNA template strand. When the cell repairs the damage produced by Cas9, it copies from the template, introducing new genetic material into the genome. Scientists envision that this kind of genome editing could one day help treat diseases such as hemophilia, Huntington's disease, and others that are caused by single mutations.

Scientists have developed other gene-editing systems based on DNA-slicing enzymes, also known as nucleases, but those complexes can be expensive and difficult to assemble.

"The CRISPR system is very easy to configure and customize," says Anderson, who is also a member of MIT's Institute for Medical Engineering and Science. He adds that other systems "can potentially be used in a similar way to the CRISPR system, but with those it is much harder to make a nuclease that's specific to your target of interest."

Disease correction

For this study, the researchers designed three guide RNA strands that target different DNA sequences near the mutation that causes type I tyrosinemia, in a gene that codes for an enzyme called FAH. Patients with this disease, which affects about 1 in 100,000 people, cannot break down the amino acid tyrosine, which accumulates and can lead to liver failure. Current treatments include a low-protein diet and a drug called NTCB, which disrupts tyrosine production.

In experiments with adult mice carrying the mutated form of the FAH enzyme, the researchers delivered RNA guide strands along with the gene for Cas9 and a 199-nucleotide DNA template that includes the correct sequence of the mutated FAH gene.

Using this approach, the correct gene was inserted in about one of every 250 hepatocytes the cells that make up most of the liver. Over the next 30 days, those healthy cells began to proliferate and replace diseased liver cells, eventually accounting for about one-third of all hepatocytes. This was enough to cure the disease, allowing the mice to survive after being taken off the NCTB drug.

"We can do a one-time treatment and totally reverse the condition," says Hao Yin, a postdoc at the Koch Institute and one of the lead authors of the Nature Biotechnology paper.

To deliver the CRISPR components, the researchers employed a technique known as high-pressure injection, which uses a high-powered syringe to rapidly discharge the material into a vein. This approach delivers material successfully to liver cells, but Anderson envisions that better delivery approaches are possible. His lab is now working on methods that may be safer and more efficient, including targeted nanoparticles.

Contact: Sarah McDonnell
Massachusetts Institute of Technology

Related biology news :

1. Genetic mutations warn of skin cancer risk
2. Drilling into the trends in genetics and epigenetics of aging and longevity
3. Faster genetic testing method will likely transform care for patients with breast cancer
4. Genetics can explain why infections can trigger rheumatoid arthritis
5. Certain genetic variants may put bladder cancer patients at increased risk of recurrence
6. MRI reveals genetic activity
7. UT Southwestern ob/gyn researchers studying genetic factors in premature births
8. Researchers issue state-of-the-state on genetic-based testing & treatment for breast cancer
9. TGen-led study discovers genetic cause of rare type of ovarian cancer
10. Genetic testing may help select women with ER+ breast cancer for extended hormone therapy
11. Genetic test could improve colon cancer screening
Post Your Comments:
(Date:10/26/2015)... and LAS VEGAS , Oct. 26, ... , an innovator in modern authentication and a founding ... the launch of its latest version of the Nok ... organizations to use standards-based authentication that supports existing and ... Authentication Suite is ideal for organizations deploying customer-facing applications ...
(Date:10/23/2015)... DUBLIN , Oct. 23, 2015 Research ... of the "Global Voice Recognition Biometrics Market 2015-2019" ... --> --> The global voice recognition ... during 2014-2019. --> ... 2015-2019, has been prepared based on an in-depth market ...
(Date:10/22/2015)...  Aware, Inc. (NASDAQ: AWRE ), a leading supplier of ... quarter ended September 30, 2015.  --> ... $4.0 million, a decrease of 33% compared to $6.0 million in ... of 2015 was $2.2 million, or $0.10 per diluted share, which ... same period a year ago.  --> ...
Breaking Biology News(10 mins):
(Date:11/24/2015)... ... , ... This fall, global software solutions leader SAP and AdVenture Capital brought ... pitch their BIG ideas to improve health and wellness in their schools. , Now, ... the title of SAP's Teen Innovator, an all-expenses paid trip to Super Bowl 50, ...
(Date:11/24/2015)... November 24, 2015 --> ... research report released by Transparency Market Research, the global ... a CAGR of 17.5% during the period between 2014 ... - Global Industry Analysis, Size, Volume, Share, Growth, Trends ... prenatal testing market to reach a valuation of US$2.38 ...
(Date:11/24/2015)... FRANCISCO , Nov. 24, 2015  Twist ... announced that Emily Leproust, Ph.D., Twist Bioscience chief ... Jaffray Healthcare Conference on December 1, 2015 at ... Hotel in New York City. --> ... . Twist Bioscience is on Twitter. ...
(Date:11/24/2015)... , ... November 24, 2015 , ... ... OrthoAccel® Technologies, Inc., on being named to Deloitte's 2015 Technology Fast 500 list ... facility, OrthoAccel manufactures AcceleDent®, a FDA-cleared, Class II medical device that speeds up ...
Breaking Biology Technology: